The human skin is the outer covering and a metabolically active organ of the human body. It is the largest organ of the integumentary system with a surface area of about 1.8 square meters in a grown adult. The skin is composed of three layers of ectodermal tissue, guards the underlying muscles, bones, ligaments and internal organs, and maintains inner homeostasis. Since it interfaces with the environment, the skin plays a key role in protecting the body against pathogens. Accordingly, almost all types of cells of the immune system can be found within the skin that can inter alia mediate a variety of allergic reactions that occur at or within the skin. The range of known skin or dermatological diseases is broad, wherein the most common include psoriasis, eczema, acne and Herpes simplex infections. In all dermatological diseases, factors such as nutrition, hygiene, UV exposure, climate, complexion, sex, age, and genetic determinants, as well as stress and psychological factors play a more or less prominent role.
Psoriasis is a chronic, non-infectious, inflammatory disease of the skin. It is characterized by sharply bounded plaques with a silvery-white scaling. The clinical picture of psoriasis is very broad, reaching from mild alterations of the skin to life-threatening systemic conditions. In over a third of the affected patients, a genetic predisposition can be determined. The disease can further be provoked or aggravated by factors such as trauma, infections, exposure to UV radiation, stress, artificial food products, alcohol, smoking, or various medicaments. Sometimes, psoriasis is accompanied by joint disorders or autoimmune conditions. Treatment of psoriasis commonly uses topical medicaments such as tar preparations, dithranol, corticosteroids, vitamin D analogues, or salicylic acid. More severe forms of the disease often have to be treated systemically using photochemical therapies, retinoids, methotrexate, hydroxyurea, azathioprine or cyclosporin. However, some of these have severe side-effects and/or are not effective in some patients. Recently, clinical studies using monoclonal antibodies or certain fusion proteins have been conducted, showing improved efficacy against psoriasis. However, the pharmacological safety of such treatments remains to be shown. In summary, treatments of more severe forms of psoriasis are costly, often show undesirable side-effects, and have a varying efficacy.
Eczemas are non-infectious, inflammatory skin diseases that can be caused by a wide range of stimuli. They are classified as exogenous eczemas, endogenous eczemas and non-classifiable eczemas. The most common exogenous eczema is known as contact dermatitis which can be caused by various substances such as chrome, cobalt, dermal patches, softening agents, lacquers, finishers, impregnating agents, adhesives, fragrances, nickel, colors and others. The treatment of contact eczema is very difficult, as long as the aggrieving allergen is not found and eliminated. Accordingly, identification of the allergen is of paramount importance. During the acute phase, corticosteroidal ointments can be used. The most common endogenous eczema is atopic eczema, also known as atopic dermatitis or neurodermitis. Atopic eczema is a chronic inflammation of the skin that is often associated with asthma, allergic rhinitis and/or conjunctivitis. Some studies suggest an involvement of allergic reactions to house dust mites and certain substances. The disease pattern is broadly diversified and symptoms are frequently regressing and recurring. Treatment of atopic eczema involves the elimination of the eliciting factor, e.g. house dust mites, animal hair, wool and other irritants, as well as the use of skin care agents, topical steroids, oral antibiotics or dietary measures. Recently, two new immunosuppressive macrolides, tacrolimus and pimecrolimus, have been investigated. Both are used topically and show a similar mechanism of action. In severe forms of atopic eczema, phototherapy, photochemotherapy, and systemic immunosuppressives such as cyclosporin A are used.
Acne is caused by inflammation of sebaceous glands. It is characterized by an increased production of sebum and a colonization of sebaceous gland ducts by bacteria. There exists a huge variety of cosmetic and pharmacological products for the treatment of acne that are applied topically. In severe forms of acne, medicaments such as antibiotics, antiandrogens, retinoids and others can be used.
Herpes simplex is an acute viral infection that is transmitted via infected subjects and can occur at various sites such as the mouth or the genitals. The disease cycles between active periods and periods of remission, wherein reactivation is mediated by factors such as e.g. stress. As no cure for herpes has been found so far, the virus persists in the body for life. Treatment of herpes involves the topical application of aciclovir-containing creams which have been shown to be able to shorten the disease periods.
Recently, it has been shown that oxidative stress plays a major role in the development and maintenance of dermatological diseases, in particular inflammatory diseases such as the ones indicated above. During normal metabolism, an adult human uses about 250 grams of oxygen per day. About 2 to 5% of this amount are converted to reactive oxygen species (ROS). These are short-lived but highly reactive molecules that have a normal physiological role in low concentrations, but can severely damage cells in higher concentrations. Therefore, the accumulation of ROS is prevented by cellular anti-oxidative systems that maintain the so-called redox-homeostasis. However, any disturbance of this homeostasis due to an increased formation of ROS and/or a decreased activity of the anti-oxidative systems can lead to oxidative stress. Oxidative stress in turn can lead to DNA damage, peroxidation of lipids, and damage of cell membranes, as well as to inflammatory immune reactions by the induction of inflammatory cytokines that are related to the pathogenesis of various inflammatory skin diseases including psoriasis, atopic dermatitis, acne and others.
In summary, dermatological diseases, in particular inflammatory diseases, pose a serious and often chronic impairment of the quality of life of the affected subjects and in extreme cases can even lead to life-threatening conditions. Many of these diseases can only be treated in a symptomatic manner, wherein treatments are often not very effective. Further, more severe cases often require the treatment with medicaments that have severe side-effects.